Compounds for the treatment and prevention of bronchial inflammatory diseases including COPD are classified in the art as bronchodilator also called reliever medications or nonbronchodilators antinflammatory agents referred to as controller agents, on the basis of their pharmacodynamic effects.
Short-acting bronchodilators such as inhaled beta agonist or anticholinergics are considered reliever medications. Corticosteroids, cromolyn sodium, nedocromil sodium, sustained-release theophylline and long-acting beta agonist are considered controller medications, since they are used to achieve and maintain control of symptoms and are used daily on a long-term basis.
Among reliever medication, inhaled 132-adrenergic agonists are drugs for relief of symptoms due to acute airway obstruction. They have a rapid onset of action and a 3-6 h duration of activity. Unfortunately they have side effects such as tachycardia, palpitations and tremor that often disapear during chronic administration.
Anticholinergic agents induce airway smooth muscle relaxation. Their activity is not as effective as beta agonists in asthma but is more prolonged (6 to 8 hours).
Among controller medications, glucocorticosteroids are effective agents with anti-inflammatory effects. Unfortunately, their side effects include adrenal suppression, osteoporosis, growth suppression, weight gain, hypertension, diabetes, dermal thinning, cataracts, myopathy and psychotic actions. These effects are dose related and are usually seen with systemic administration. Local side effects, including oral candidiasis and dysphonia may occur at lower doses of inhaled glucocorticoids.
Cromolyn sodium and nedocromil sodium are also classified as controller agents, because of their similar clinical profile. They inhibit bronchoconstriction induced by neurally mediated events.
Theophylline is generally considered as a bronchodilator but has weak bronchodilator activity in therapeutic doses. It may also have anti-inflammatory properties. The dose-related adverse effects of theophylline are nausea, nervousness, anxiety and tachycardia.
Lipoxygenase inhibitors and leukotriene receptor agonists are also controller agents. They alter the pathological effects of leukotrienes derived from the 5-lipoxygenation of arachidonic acid. They can inhibit the bronchospastic effects of allergens, exercice, cold dry air, and aspirin allergy. Both are efficaceous in alleviating symtoms and improving pulmonary function during 4-6 weeks of therapy in patients with moderate asthma.
There is therefore a need for improved compounds which can be used for the treatment or prevention of bronchial inflammatory diseases including COPD.